Generalized natural boundary conditions for fractional variational problems in terms of the Caputo derivative

This paper presents the necessary and sufficient optimality conditions for problems of the fractional calculus of variations with a Lagrangian depending on the free end-points. The fractional derivatives are defined in the sense of Caputo.     

Chemerin Affects P4 and E2 Synthesis in the Porcine Endometrium during Early Pregnancy

Chemerin, belonging to the adipokine family, exhibits pleiotropic activity. We hypothesised that the adipokine could be involved in the regulation of steroidogenesis in the porcine endometrium. Thus, the aim of this study was to determine the effect of chemerin on the key steroidogenic enzyme proteins’ abundance (Western blot), as well as on P₄ and E₂ secretion (radioimmunoassay) by the porcine endometrium during early pregnancy and the mid-luteal phase of the oestrous cycle. Moreover, we investigated the hormone impact on Erk and Akt signalling pathway activation (Western blot). Chemerin stimulated E₂ production on days 10 to 11 of pregnancy. On days 10 to 11 and 15 to 16 of gestation, and on days 10 to 11 of the cycle, chemerin enhanced the expression of StAR and all steroidogenic enzyme proteins. On days 12 to 13 of pregnancy, chemerin decreased StAR and most of the steroidogenic enzyme proteins’ abundance, whereas the P450_C17 abundance was increased. On days 27 to 28 of pregnancy, chemerin increased StAR and P450_C17 protein contents and decreased 3βHSD protein amounts. It was noted that the adipokine inhibited Erk1/2 and stimulated Akt phosphorylation. The obtained results indicate that chemerin affected P₄ and E₂ synthesis through the Erk1/2 and Akt signalling pathways.     

Lichtenstein inguinal hernia repair in a primary healthcare setting

BACKGROUND: Given the generally accepted poor outcome of inguinal hernia repair when using nylon darn, and the recent interest in low-tension mesh repair, an attempt was made to demonstrate the feasibility, outcome and patient perception of providing Lichtenstein inguinal hernia repair, using local anaesthesia, wholly within the primary healthcare sector. METHODS: A prospective study reviewed clinical outcome and patient perception in 100 adults referred with inguinal hernia only. No selection was made regarding age, sex, American Society of Anesthesiologists status or previous repairs. Recurrence, pain, infection, return to full function and associated complications were assessed at 24 h, 1 and 6 weeks, and 1 year. Local Community Health Councils assessed patient perception. RESULTS: In the first 100 patients (age range 21-83 (mean(s.d.) 60(14.7)) years; 58 of employable age; 92 men; ten recurrent hernias), no recurrences have occurred at 1 year. Infection rate was 3 per cent. Pain was maximal in the first 24-48 h (median visual analogue scale 5, range 0-10) and reduced rapidly (median 1) at 1 week. Mean time to return to work or full normal activity was 8 days. Some 85 operations were performed within 1 month of diagnosis. In all, 86 patients returned the patient satisfaction questionnaire and 98 per cent of these were 'very pleased' with the service. CONCLUSION: In highly motivated primary healthcare centres, inguinal hernia repair can be undertaken effectively, providing high patient satisfaction, minimal complications and low recurrence rates using the Lichtenstein technique.     

Development of microfibers for bone regeneration based on alkali-free bioactive glasses doped with boron oxide

In this paper, we present a new series of alkali-free bioactive glasses (BG) based on FastOs^® composition (38.49 SiO₂ – 36.07 CaO – 19.24 MgO – 5.61 P₂O₅ – 0.59 CaF₂, expressed in mol %), which was modified by partially replacing silicon dioxide network-former with boron trioxide network-former, utilizing calcium oxide as a charge compensator. The main objective of this study was to obtain a new family of bioactive glasses suitable for the fabrication of glass fibers. The BGs were prepared by melt quenching technique and their structural and thermal properties were determined. Glass rods were used to obtain fibers by the classic drawing technique. The bioactivity of the fibers was subsequently assessed through immersion tests in simulated body fluid (SBF) to establish their ability to form hydroxyl carbonated (HCA) apatite onto their surfaces. Glasses with moderate substitution of SiO₂ with B₂O₃ exhibited enhanced thermal properties, allowing to significantly suppress the crystallization trend, and favoring to draw the fibers. The structure of the studied glasses was obtained by NMR spectroscopy. The structure-property correlations were established by their relationship to the configurational entropy. Smaller amounts of substitution resulted in larger entropy of the glasses. Moreover the SBF tests revealed an extensive formation of HCA, comparable to the parent FastOs^®BG composition, which assures fast bonding to the bone. Thus, presented glass fibers may be considered as promising materials for wool-like bone implants or as reinforcing constituent of biopolymer matrix composites.     

COVID-19: Direct and Indirect Mechanisms of Statins

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-β and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.     

Effects of Metallic and Carbon-Based Nanomaterials on Human Pancreatic Cancer Cell Lines AsPC-1 and BxPC-3

Pancreatic cancer, due to its asymptomatic development and drug-resistance, is difficult to cure. As many metallic and carbon-based nanomaterials have shown anticancer properties, we decided to investigate their potential use as anticancer agents against human pancreatic adenocarcinoma. The objective of the study was to evaluate the toxic properties of the following nanomaterials: silver (Ag), gold (Au), platinum (Pt), graphene oxide (GO), diamond (ND), and fullerenol (C₆₀(OH)₄₀) against the cell lines BxPC-3, AsPC-1, HFFF-2, and HS-5. The potential cytotoxic properties were evaluated by the assessment of the cell morphology, cell viability, and cell membrane damage. The cancer cell responses to GO and ND were analysed by determination of changes in the levels of 40 different pro-inflammatory proteins. Our studies revealed that the highest cytotoxicity was obtained after the ND treatment. Moreover, BxPC-3 cells were more sensitive to ND than AsPC-1 cells due to the ND-induced ROS production. Furthermore, in both of the cancer cell lines, ND caused an increased level of IL-8 and a decreased level of TIMP-2, whereas GO caused only decreased levels of TIMP-2 and ICAM-1 proteins. This work provides important data on the toxicity of various nanoparticles against pancreatic adenocarcinoma cell lines.     

Comparative Evaluation of Different Surface Coatings of Fe3O4-Based Magnetic Nano Sorbent for Applications in the Nucleic Acids Extraction

Nucleic acid extraction and purification are crucial steps in sample preparation for multiple diagnostic procedures. Routine methodologies of DNA isolation require benchtop equipment (e.g., centrifuges) and labor-intensive steps. Magnetic nanoparticles (MNPs) as solid-phase sorbents could simplify this procedure. A wide range of surface coatings employs various molecular interactions between dsDNA and magnetic nano-sorbents. However, a reliable, comparative evaluation of their performance is complex. In this work, selected Fe₃O₄ modifications, i.e., polyethyleneimine, gold, silica, and graphene derivatives, were comprehensively evaluated for applications in dsDNA extraction. A family of single batch nanoparticles was compared in terms of morphology (STEM), composition (ICP-MS/MS and elemental analysis), surface coating (UV-Vis, TGA, FTIR), and MNP charge (ζ-potential). ICP-MS/MS was also used to unify MNPs concentration allowing a reliable assessment of individual coatings on DNA extraction. Moreover, studies on adsorption medium (monovalent vs. divalent ions) and extraction buffer composition were carried out. As a result, essential relationships between nanoparticle coatings and DNA adsorption efficiencies have been noticed. Fe₃O₄@PEI MNPs turned out to be the most efficient nano sorbents. The optimized composition of the extraction buffer (medium containing 0.1 mM EDTA) helped avoid problems with Fe³⁺ stripping, which improved the validity of the spectroscopic determination of DNA recovery.     

Densitometric determination of carbohydrates: Application to purification and molecular weight determination of polysaccharide from Hericium erinaceum mushroom

A simple, precise, sensitive and quick densitometric method for quantitative total carbohydrate determination as well as for preparation of elution profiles of polysaccharides was developed and validated. The method is based on spotting 3 μL of sample solution by use of disposable micro capillary pipettes as a single drop on a TLC silica gel plate. The plate is then submitted to in situ derivatization with orcinol–sulfuric acid reagent and is scanned densitometrically at 560 nm (for hexoses, deoxy sugars, and uronic acids) or at 610 nm (for pentoses and ketoses). It was demonstrated that the densitometric method has a greater linearity range and similar precision in comparison to the widely used colorimetric phenol–sulfuric acid method. The proposed method was successfully applied to elution profile preparation during purification and molecular weight determination of a novel polysaccharide isolated from the mycelium of edible and medicinal mushroom Hericium erinaceum.     

Visualisation of morphological interaction of diamond and silver nanoparticles with Salmonella Enteritidis and Listeria monocytogenes

Currently, medicine intensively searches for methods to transport drugs to a target (sick) point within the body. The objective of the present investigation was to evaluate morphological characteristics of the assembles of silver or diamond nanoparticles with Salmonella Enteritidis (G-) or Listeria monocytogenes (G+), to reveal possibilities of constructing nanoparticle-bacteria vehicles. Diamond nanoparticles (nano-D) were produced by the detonation method. Hydrocolloids of silver nanoparticles (nano-Ag) were produced by electric non-explosive patented method. Hydrocolloids of nanoparticles (200 microl) were added to bacteria suspension (200 microl) in the following order: nano-D + Salmonella E.; nano-D + Listeria monocytogenes; nano-Ag + Salmonella E; nano-Ag + Listeria monocytogenes. Samples were inspected by transmission electron microscopy. Visualisation of nanoparticles and bacteria interaction showed harmful effects of both nanoparticles on bacteria morphology. The most spectacular effect of nano-D were strong links between nano-D packages and the flagella of Salmonella E. Nano-Ag were closely attached to Listeria monocytogenes but not to Salmonella E. There was no evidence of entering nano-Ag inside Listeria monocytogenes but smaller particles were placed inside Salmonella E. The ability of nano-D to attach to the flagella and the ability of nano-Ag to penetrate inside bacteria cells can be utilized to design nano-bacteria vehicles, being carriers for active substances attached to nanoparticles.